Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTREV92I)

• DOT Name: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)
• Synonyms: Carcinoembryonic antigen; CEA; Meconium antigen 100; CD antigen CD66e
• Gene Name: CEACAM5
• UniProt ID: CEAM5_HUMAN
• PDB ID: 1E07; 2QSQ; 2QST; 2VER
• Pfam ID: PF13895 ; PF13927 ; PF07686
• Sequence:
  MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
  HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFY
  TLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
  NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDAP
  TISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTCQ
  AHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNN
  QSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTI
  SPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQAN
  NSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQS
  LPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP
  PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNL
  ATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
• Function: Cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM6. Plays a role as an oncogene by promoting tumor progression; induces resistance to anoikis of colorectal carcinoma cells ; (Microbial infection) Receptor for E.coli Dr adhesins. Binding of E.coli Dr adhesins leads to dissociation of the homodimer.
• Tissue Specificity: Expressed in columnar epithelial and goblet cells of the colon (at protein level) . Found in adenocarcinomas of endodermally derived digestive system epithelium and fetal colon.
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[1]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[7]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[12]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[13]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).	[9]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [3] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [8] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Cancer-related proteins in serum are altered in workers occupationally exposed to polycyclic aromatic hydrocarbons: a cross-sectional study. Carcinogenesis. 2019 Jul 6;40(6):771-781. doi: 10.1093/carcin/bgz022.